This invention relates to cephalosporin antibiotics, to pharmaceutical formulations thereof, and to a method for treating bacterial infections. In particular, it relates to cephalosporin antibiotics which structurally possess a 7-[2-(amino-substituted 5- or 6-membered heterocyclic ring)-2-oximinoacetylamino] side chain and a bicyclic pyridinium-methyl group in the 3-position of the cephalosporin nucleus.
Prior to this invention, a number of cephalosporin antibiotics substituted in the 3-position by a quaternary ammonium methyl and in the 7-position with various acylamino groups were known. Such compounds possess the betaine structure in that the positively-charged nitrogen atom of the quaternary ammonium group exists in the salt form with the anionic form of the C.sub.4 carboxy group (carboxylate anion) of the cephalosporin. The well-known cephalosporin antibiotic cephaloridine, 7-(.alpha.-thienylacetamido)-3-(pyridinium-1-ylmethyl)-3-cephem-4-carboxyl ate of the following formula, possesses the betaine structure. ##STR1##
The first cephalosporin of this structural type was discovered by Hale, Newton, and Abraham, Biochem. J. 79, 403 (1961), upon the reaction of cephalosporin C with pyridine (cephalosporin C.sub.A). Numerous other cephalosporin betaines with differing 7-acylamino side chains have been described since cephalosporin C.sub.A and cephaloridine were discovered.
Recently, Heymes et al., U.S. Pat. No. 4,152,432, described cephalosporin antibiotics having as the 7-acylamino side chain a 7-[2-(2-aminothiazol-4-yl)-2-alkoxyiminoacetylamino] group and as the 3-position substituent an acetoxymethyl group. Others have prepared betaine derivatives of this antibiotic, e.g., as described in U.S. Pat. No. 4,098,888, by Takeda and in U.S. Pat. No. 4,258,041, by O'Callaghan et al.
Because the cephalosporin antibiotics possess potent antibacterial activity, intensive research in efforts to find improved broad spectrum cephalosporin antibiotics continues. In particular, these efforts seek improved cephalosporin antibiotics having potent broad spectrum activity coupled with activity against bacteria and bacterial strains known to be resistant to antibiotics in current use. An object of this invention is to provide a new group of cephalosporins having excellent broad spectrum activity.